The parotid secretory protein BPIFA2 is a salivary surfactant that affects lipopolysaccharide action

Abstract

Saliva plays important roles in the mastication, swallowing and digestion of food, speech and lubrication of the oral mucosa, antimicrobial and anti-inflammatory activities, and the control of body temperature in grooming animals. The salivary protein BPIFA [BPI fold containing family A member 2; former names: parotid secretory protein (PSP), SPLUN2 and C20orf70] is related to lipid-binding and lipopolysaccharide (LPS)-binding proteins expressed in the mucosa. Indeed, BPIFA2 binds LPS, but the physiological role of BPIFA2 remains to be determined. To address this question, Bpifa2 knockout (Bpifa2 tm1(KOMP)Vlcg) (KO) mice were phenotyped, with emphasis on the saliva and salivary glands. Stimulated whole saliva collected from KO mice was less able to spread on a hydrophobic surface than wild-type saliva, and the surface tension of KO saliva was close to that of water. These data suggest that BPIFA2 is a salivary surfactant that is mainly responsible for the low surface tension of mouse saliva. The reduced surfactant activity of KO saliva did not affect consumption of dry food or grooming, but saliva from KO mice contained less LPS than wild-type saliva. Indeed, mice lacking BPIFA2 responded to ingested LPS with an increased stool frequency, suggesting that BPIFA2 plays a role in the solubilization and activity of ingested LPS. Consistent with these findings, BPIFA2-depleted mice also showed increased insulin secretion and metabolomic changes that were consistent with a mild endotoxaemia. These results support the distal physiological function of a salivary protein and reinforce the connection between oral biology and systemic disease.

Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross

“…Bpifb2 is a member of the lipid-transfer protein family and is predicted to have bactericidal and permeability-increasing properties, making it a promising candidate for further investigation [ 66 ]. While preliminary RNA-seq results do not show a significant difference between survived and susceptible mice, Bpifb2 ’s family member Bpifa2 is more highly expressed in surviving mice than susceptible mice and binds LPS and acts as a bactericide, suggesting this family of proteins is important to the bacterial immune response [ 67 , 68 ]. Samhd1 regulates interferon pathways in response to viral infections through NF-KB [ 69 , 70 ].…”

Proteomic and microbiota analyses of the oral cavity during psychological stress

“…BPIFA2 or Parotid Secretory Protein is a palate, lung, and nasal epithelial clone family protein and is expressed in human salivary glands, constituting ~0.5% of the total proteins in human saliva [ 27 ]. BPIFA2 has been shown to function as a salivary surfactant; the saliva from a BPIFA2 knock-out mouse demonstrated diminished ability to spread on the surface when compared to that from a wild-type mouse [ 28 ]. The increase in the level of BPIFA2 under psychological stress indicates that stress might increase the surfactant property of saliva.…”

Identification of the Major Protein Components of Human and Cow Saliva

“…This very abundant protein has been proposed to play a role in local antibacterial response by binding bacterial lipopolysaccharides (LPSs) and inhibiting bacterial growth [13]. However, recently, the role of this protein in bacterial defense has been questioned [18]. The protein may instead have a major function as a surfactant to facilitate the rumination by its surface activity to quickly wet the digested material for efficient degradation by enzymes of the microbial flora of the rumen [18].…”